Abstract
Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.
Highlights
Oxygen homeostasis involves several tissues and organs, including the heart, lungs, bone marrow and blood
Erythrocytosis is a rare hematological disorder that arises from an imbalance in homeostatic mechanisms of erythropoiesis and oxygen homeostasis
This review aimed to discover additional molecular mechanisms correlated with erythropoiesis and erythrocytosis
Summary
Oxygen homeostasis involves several tissues and organs, including the heart, lungs, bone marrow and blood. After excluding the mutation in JAK2, patients with persistent erythrocytosis from a young age or with a family history are usually screened for mutations in 9 genes involved in oxygen sensing in kidneys (EPOR, VHL, EGLN1, EPAS1, EPO), erythropoietin signal transduction in pre-erythrocytes (EPOR) and hemoglobin-oxygen affinity regulation in mature erythrocytes (HBB, HBA, BPGM). Understanding the main regulatory pathways in the process of oxygen homeostasis is necessary to identify new potential factors, which have not been yet associated with erythrocytosis but could contribute to its development. This can further improve the diagnostic methods for prompt and accurate diagnosis and selection of appropriate treatment. The revision of metabolism is necessary, as modulation of glucose and iron metabolism was confirmed to be involved in the development of erythrocytosis [11,12]
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